Efficient and selective hydroarylation of propiolic acids and their esters with arenes catalyzed by a PtCl2/AgOTf system

Article abstract of DOI:10.1016/j.tetlet.2005.03.179

PtCl₂/AgOTf-catalyzed hydroarylation of ethyl propiolate proceeded effectively to give ethyl (2Z)-cinnamate derivatives in good to high yields, without the formation of diethyl (1E,3Z)-4-arylbuta-1,3-diene-1,3- dicarboxylates that was observed in Pd(OAc)₂-catalyzed reaction. Especially, PtCl₂/AgOTf-catalyzed hydroarylation of propiolic acids proceeded effectively to give (2Z)-cinnamic acids exclusively.

Full text of DOI:10.1016/j.tetlet.2005.03.179

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 3823–3827
Efficient and selective hydroarylation of propiolic acids and
their esters with arenes catalyzed by a PtCl2/AgOTf system
Juzo Oyamada and Tsugio Kitamura*
Department of Chemistry and Applied Chemistry, Faculty of Science and Engineering, Saga University,
1 Honjo-machi, Saga 840-8502, Japan
Received 3 February 2005; revised 23 March 2005; accepted 29 March 2005
Available online 13 April 2005
Abstract—PtCl2/AgOTf-catalyzed hydroarylation of ethyl propiolate proceeded effectively to give ethyl (2Z)-cinnamate derivatives
in good to high yields, without the formation of diethyl (1E,3Z)-4-arylbuta-1,3-diene-1,3-dicarboxylates that was observed in
Pd(OAc)2-catalyzed reaction. Especially, PtCl2/AgOTf-catalyzed hydroarylation of propiolic acids proceeded effectively to give
(2Z)-cinnamic acids exclusively.
Ó 2005 Elsevier Ltd. All rights reserved.
Catalytic C–H bond activation followed by functionali-
zation has attracted much attention.1 The pro-
cess provides a direct and environmentally-benign
transformation because it does not require pre-function-
alization like halogenation. Hydroarylation of alkynes
via aromatic C–H bond activation is one of the most
atom-economic processes. The reaction has been studied
widely by using various transition metal catalysts.2–10
1,3-dicarboxylates caused decrease of the yield of the
expected cinnamates because 2 equiv of ethyl propiolate
is consumed by the formation of the buta-1,3-diene-1,3-
dicarboxylates. Therefore, a selective reaction that does
not give the buta-1,3-diene-1,3-dicarboxylates is re-
quired for increasing the yield of the cinnamates. Nolan
and co-workers reported that the N-heterocyclic carbene
palladium complexes also catalyzed the hydroarylation
reaction under the same reaction conditions as
Pd(OAc)2 catalysis and the reaction gave the cinnamates
selectively, suppressing the formation of the buta-1,3-
diene-1,3-dicarboxylates.2i We also showed that the
hydroarylation of ethyl propiolate catalyzed by PtCl2/
AgOAc proceeds selectively, without the formation of
the buta-1,3-diene-1,3-dicarboxylates.3 In our continu-
ous study of the hydroarylation, it was found that the
activity of the PtCl2/AgOAc catalyst was low and should
be improved. In this paper, we report a more efficient
and active PtCl2/AgOTf catalyst in the hydroarylation
of propiolates.
ð1Þ
Previously, we reported the hydroarylation of alkynes
by using a catalytic amount of Pd(OAc)2 in trifluoroace-
tic acid (TFA) as solvent (Eq. 1).2c–h,3 The reaction gave
aryl-substituted alkenes with high regio- and stereoselec-
tivity in good to high yield. However, the hydroaryla-
tion of ethyl propiolate give diethyl (1E,3Z)-4-
arylbuta-1,3-diene-1,3-dicarboxylate derivatives along
with the expected product, ethyl (2Z)-cinnamates,
although the yields of the buta-1,3-diene-1,3-dicarboxy-
lates were low.2c,3 The formation of the buta-1,3-diene-
Keywords: Hydroarylation; Propiolic acid; Platinum chloride; Silver
triflate; C–H Bond functionalization; Trifluoroacetic acid.
*
Corresponding author. Tel.: +81 952 28 8550; fax: +81 952 28
8548; e-mail: kitamura@cc.saga-u.ac.jp
ð2Þ
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.03.179

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J. Oyamada, T. Kitamura / Tetrahedron Letters 46 (2005) 3823–3827
First, we investigated silver compounds as additives that
were expected to react with PtCl2, affording a more cat-
ionic Pt species. This investigation was carried out in the
reaction of ethyl propiolate (2a) with mesitylene (1a)
that gave moderate yield in the case of the Pd(OAc)2 cat-
alyst (Eq. 2). The results are listed in Table 1.11 The
PtCl2/AgOAc-catalyzed reaction gave ethyl (2Z)-3-(2,4,6-
trimethylphenyl)propenoate (3a) and ethyl (2Z)-3-{3-
[(1Z)-2-ethoxycarbonylethenyl]-2,4,6-trimethylphenyl}-
propenoate (4a) in 36.4% and 1.0 % yield, respectively
(entry 1), while the reaction did not proceed without cat-
alyst (entry 2). The reaction did not gave diethyl
(1E,3Z)-4-(2,4,6-trimethylphenyl)buta-1,3-diene-1,3-di-
carboxylate (5a), similar to the previous report.3 How-
ever, the yield and the conversion were low and almost
same as those obtained when only PtCl2 was used
Table 1. Pt(II)-catalyzed hydroarylation of ethyl propiolate (2a) with mesitylene (1a)a
Entry
Catalysts
(Mol%)
Conversion of 1a/%
Yields/%b
3a
4a
5a
1
PtCl2/AgOAc
None
(2.5/5.0)
41.1
0.7
36.4
0
1.0
0
0
2
0
3
PtCl2
(2.5)
43.2
43.6
50.9
76.3
78.0
83.8
20.3
72.9
—
39.2
40.5
43.5
64.3
65.6
67.4
13.3
51.0
85.7d
1.9
1.3
1.9
9.1
10.8
15.7
0
0
4
PtCl2/AgTFAc
PtCl2/Ag2CO3
PtCl2/AgPF6
PtCl2/AgBF4
PtCl2/AgOTf
AgOTf
(2.5/5.0)
(2.5/2.5)
(2.5/5.0)
(2.5/5.0)
(2.5/5.0)
(5.0)
0
5
0
6
0
7
0
8
0
9
0
10
11
Pd(OAc)2
PtCl2/AgOTf
(2.5)
(2.5/5.0)
2.1
11.9d
9.6
0
a Reaction conditions: mesitylene (1a) (2 mmol), ethyl propiolate (2a) (2.4 mmol), catalysts, TFA (1 mL), room temperature, 15 h.
b GC yields based on 1a.
c AgTFA = AgOCOCF3.
d 1a (4 mmol) and 2a (2 mmol) were used. The yields based on 2a.
Table 2. Hydroarylation of ethyl propiolate (2a) with various arenesa
Entry
Ar–H
Temp
Time/h
15
Products and yields/%b
91.1 (95.4)c
1
RT
2
3
4
RT
35
40
48
64.5d
RT
61.4 (61.6) (Z/E = 99/<1)
40 °C
63.9 (64.9)e
5
RT
48
76.2f
a Reaction conditions: PtCl2 (0.05 mmol), AgOTf (0.10 mmol), arene (4 mmol), ethyl propiolate (2a) (2 mmol), TFA (1 mL).
b Isolated yields based on 2a. The yields in parentheses were determined by GC.
c CH2Cl2 (0.25 mL) was added.
d CH2Cl2 (0.5 mL) was added. 6b was obtained in <8% yield.
e CH2Cl2 (0.5 mL) and ClCH2CH2Cl (0.5 mL) were added. 4b and 6c were isolated in 4.4% and 12.8% yield, respectively.
f 4c was isolated in 14.0% yield.

J. Oyamada, T. Kitamura / Tetrahedron Letters 46 (2005) 3823–3827
3825
(entry 3). Addition of AgOCOCF3 did not affect the rea-
ction (entry 4). Ag2CO3 slightly improved the yield and
the conversion (entry 5). AgPF6 and AgBF4 were effec-
tive (entries 6 and 7) but AgOTf was the best additive
among the Ag compounds tested (entry 8). PtCl2/AgOTf
catalyst gave the highest conversion and yields among
the employed Pd and Pt catalysts, revealing the effectiv-
ity of PtCl2/AgOTf catalyst. The reaction also proceeded
by using only AgOTf in the absence of PtCl2 (entry 9)
but the yield was very low. This result suggests that
the active catalyst is the Pt species generated from the
reaction of AgOTf and PtCl2. The role of AgOTf is con-
sidered to transform insoluble PtCl2 to a soluble reac-
tive, cationic Pt species.
Then, the reaction using PtCl2/AgOTf catalyst was
investigated to optimize the reaction conditions. Pro-
longed time improved the conversion of 1a to give a
Table 3. Hydroarylation of ethyl phenylpropiolatea
Entry
Ar–H
Temp
Time/h
48
Products and isolated yields/%b
1
40 °C
59.4c
2
RT
50
80.4d
a Reaction conditions: PtCl2 (0.05 mmol), AgOTf (0.10 mmol), arene (4 mmol), ethyl phenylpropiolate (2b) (2 mmol), TFA (1 mL).
b The yields were based on 2b.
c 1-Mesityl-1-phenylethene (9) was also obtained in 7.3% yield.
d CH2Cl2 (0.25 mL) was added.
.
Table 4. Hydroarylation of propiolic acidsa
Entry
1
Ar–H
R
Temp
RT
Time/h
15
Products and yields/%b
H
2c
94.3c
95.7d
76.7e
48.1f
86.1g
2
3
4
5
H
2c
RT
15
40
48
25
H
2c
40 °C
RT
Ph
2d
H
2c
RT
6
nC5H11
2e
40 °C
45
92.8
a Reaction conditions: PtCl2 (0.05 mmol), AgOTf (0.10 mmol), arene 1 (4 mmol), propiolic acids 2 (2 mmol), TFA (1 mL).
b Isolated yields based on 2.
c 1a (6 mmol) was used.
d CH2Cl2 (0.25 mL) was added.
e ClCH2CH2Cl (0.75 mL) was added.
f CH2Cl2 (0.5 mL) was added.
g CH2Cl2 (0.75 mL) was added.

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J. Oyamada, T. Kitamura / Tetrahedron Letters 46 (2005) 3823–3827
higher yield of 4a. Higher temperature also increased the
conversion of 1a but the yields of 3a and 4a were de-
creased. This observation can be explained by hydrolysis
of the ester products to acids at a higher temperature in
TFA. Using an excess amount of 1a is effective for the
selective formation of 3a. When the reaction of 1a
(4 mmol) with 2a (2 mmol) was conducted under the
same conditions, 3a and 4a were formed in 85.7% and
11.9% yields, respectively (entry 11).
References and notes
1. (a) Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. Rev. 2002,
102, 1731–1769; (b) Dyker, G. Angew. Chem., Int. Ed.
1999, 38, 1698–1712; (c) Kakiuchi, F.; Chatani, N. Adv.
Synth. Catal. 2003, 345, 1077–1101; (d) Kakiuchi, F.;
Murai, S. Activation of C–H bonds: Catalytic Reactions.
In Activation of Unreactive Bonds and Organic Synthesis;
Murai, S., Ed.; Berlin: Springer, 1999, pp 47–79; (e)
Shilov, A. E.; ShulÕpin, G. B. Chem. Rev. 1997, 97, 2879–
2932; (f) Jia, C.; Kitamura, T.; Fujiwara, Y. Acc. Chem.
Res. 2001, 34, 633–639; (g) Kakiuchi, F.; Murai, S. Acc.
Chem. Res. 2002, 35, 826–834; (h) Crabtree, R. H. J.
Chem. Soc., Dalton Trans. 2001, 2437–2450; (i) Guari, Y.;
Sabo-Etienne, S.; Chaudret, B. Eur. J. Inorg. Chem. 1999,
1047–1055.
2. (a) Pd: Trost, B. M.; Toste, F. D. J. Am. Chem. Soc. 1996,
118, 6305–6306; (b) Trost, B. M.; Toste, F. D.; Greenman,
K. J. Am. Chem. Soc. 2003, 125, 4518–4526; (c) Jia, C.;
Piao, D.; Oyamada, J.; Lu, W.; Kitamura, T.; Fujiwara,
Y. Science 2000, 287, 1992–1995; (d) Jia, C.; Piao, D.;
Kitamura, T.; Fujiwara, Y. J. Org. Chem. 2000, 65, 7516–
7522; (e) Lu, W.; Jia, C.; Kitamura, T.; Fujiwara, Y. Org.
Lett. 2000, 2, 2927–2930; (f) Oyamada, J.; Jia, C.;
Fujiwara, Y.; Kitamura, T. Chem. Lett. 2002, 31, 380–
381; (g) Kitamura, T.; Yamamoto, K.; Oyamada, J.; Jia,
C.; Fujiwara, Y. Bull. Chem. Soc. Jpn. 2003, 76, 1889–
1895; (h) Kotani, M.; Yamamoto, K.; Oyamada, J.;
Fujiwara, Y.; Kitamura, T. Synthesis 2004, 1466–1470; (i)
Viciu, M. S.; Stevens, E. D.; Petersen, J. L.; Nolan, S. P.
Organometallics 2004, 23, 3752–3755; (j) Tsukada, N.;
Mitsuboshi, T.; Setoguchi, H.; Inoue, Y. J. Am. Chem.
Soc. 2003, 125, 12102–12103.
Next, we examined the reaction with various arenes
(Table 2).11 The result showed that the reaction gave
the hydroarylated products in good to excellent yields.
Especially, electron-rich arene-like pentamethylbenzene
(1b) gave high yield of the product 3b (entry 1). The
reactions of naphthalene (1c) and p-xylene (1d) also gave
adducts 3c and d in good yields (entries 2 and 3). This
reaction is tolerant to unprotected OH and Br groups.
The reaction of 1-bromo-2,4,6-trimethylbenzene (1e)
and 2,4,6-trimethylphenol (1f) gave adducts 3e and f in
good yields, together with bis-alkenylated products 4b
and c (entries 4 and 5). In the case of 1e, higher temper-
ature was required to improve the yield because of low
reactivity of 1e (entry 4). The yields of 3 in PtCl2/
AgOTf catalysis were higher than those in Pd(OAc)2
catalysis.
Also, this reaction was applied to the reaction of inter-
nal alkyne, ethyl phenylpropiolate (2b) (Table 3). The
reaction of 2b was slower than that of 2a and longer
reaction time was required for high conversion of 2b.
The reaction mainly gave products 8 which were formed
by hydrolysis of 7 during the reaction, along with esters
7. In the case of mesitylene (1a), a small amount of
decarboxylated product 9 was observed (entry 1).
3. Pd and Pt: Jia, C.; Lu, W.; Oyamada, J.; Kitamura, T.;
Matsuda, K.; Irie, M.; Fujiwara, Y. J. Am. Chem. Soc.
2000, 122, 7252–7263.
4. (a) Pt: Pastine, S. J.; Youn, S. W.; Sames, D. Org. Lett.
2003, 5, 1055–1058; (b) Pastine, S. J.; Youn, S. W.; Sames,
D. Tetrahedron 2003, 59, 8859–8868.
5. (a) Au: Reetz, M. T.; Sommer, K. Eur. J. Org. Chem.
2003, 3485–3496; (b) Shi, Z.; He, C. J. Org. Chem. 2004,
69, 3669–3671.
6. (a) Ru: Kakiuchi, F.; Yamamoto, Y.; Chatani, N.; Murai,
S. Chem. Lett. 1995, 681–682; (b) Harris, P. W. R.;
Richard, C. E. F.; Woodgate, P. D. J. Organomet. Chem.
1999, 589, 168–179.
7. Ru and Rh: Kakiuchi, F.; Sato, T.; Tsujimoto, T.;
Yamauchi, M.; Chatani, N.; Murai, S. Chem. Lett. 1998,
1053–1054.
8. Rh: Lim, Y.-G.; Lee, K.-H.; Koo, B. T.; Kang, J.-B.
Tetrahedron Lett. 2001, 42, 7609–7612.
9. Ir: Satoh, T.; Nishiyama, Y.; Miura, M.; Nomura, M.
Chem. Lett. 1999, 615–616.
10. In, Zr and Sc: Tsuchimoto, T.; Maeda, T.; Shirakawa, E.;
Kawakami, Y. Chem. Commun. (Cambridge, UK) 2000,
1573–1574.
11. General procedure for PtCl2/AgOTf-catalyzed hydroaryla-
tion of propiolates: after a mixture of PtCl2, AgOTf, arene
and TFA was stirred for 5 min at room temperature,
propiolate was added to the mixture. The mixture was
continuously stirred at the desired temperature. After a
certain period, the reaction mixture was poured into water
(20 mL), neutralized by NaHCO3 and extracted with
diethyl ether (20 mL) three times. The ethereal layer was
dried over anhydrous Na2SO4 and concentrated in vacuo.
The residue was purified by column chromatography on
silica gel using a mixture of ethyl acetate and hexane as
eluent. 1H and 13C NMR spectra of 3a–f, 4a, 7a and b, 8a
and b were identical to those in previous reports.3
Furthermore, we conducted the hydroarylation of pro-
piolic acids because the prolonged reaction of ethyl pro-
piolates mainly gave the hydrolysis products. This
catalytic system was found to be effective for the reac-
tion of propiolic acids (Table 4).12 The reactions of pro-
piolic acid (2c) gave the corresponding cinnamic acids 6
in good to high yields. The reactions of 1a and b gave
high yield of 6a and d, respectively. In the case of mesit-
ylene (1a), 3 equiv of 1a was used to increase the selec-
tivity of 6a (entry 1). The reaction of naphthalene (1c)
at 40 °C gave 6b in 76.7% yield (entry 3). The reaction
of phenylpropiolic acid (2d) gave a moderate yield of
8b because of low solubility of 2d (entry 4). 2-Naphthol
(1j) reacted with propiolic acid (2c), affording the corre-
sponding coumarin 10a (entry 5). Alkyl-substituted pro-
piolic acid, 2-octynoic acid (2e), also participated in the
reaction (entry 6).
In conclusion, we have demonstrated selective and effi-
cient hydroarylation of propiolates catalyzed by a PtCl2/
AgOTf system. In the case of ethyl propiolate, the
PtCl2/AgOTf-catalyzed hydroarylation gave higher yield
of cinnamates than the Pd(OAc)2-catalyzed reaction be-
cause of higher selectivity of the Pt catalyst. Especially,
this catalyst was most effective for the reaction of propi-
olic acids. Further investigation of Pt-catalyzed hydro-
arylation of alkynes is now in progress.

J. Oyamada, T. Kitamura / Tetrahedron Letters 46 (2005) 3823–3827
3827
Compound 4b: oil 1H NMR (300 MHz, CDCl3): d 1.11 (t,
J = 7.1 Hz, 6H, CH3), 2.02 (s, 3H, aryl-CH3), 2.32 (s, 6H,
aryl-CH3), 4.02 (q, J = 7.1 Hz, 4H, OCH2), 6.14 (d,
J = 11.7 Hz, 2H, vinyl), 7.04 (d, J = 11.7 Hz, 2H, vinyl).
13C NMR (75 MHz, CDCl3): d 13.92, 17.82, 21.76, 60.06,
123.24, 125.87, 129.91, 133.52, 134.37, 144.04, 165.11. MS
(EI, m/z): 396, 394 (M+). Compound 4c: mp 109.3–
acidified by aqueous HCl (60%) and extracted with CH2Cl2
(20 mL) three times. The CH2Cl2 layer was dried over
anhydrous Na2SO4 and concentrated in vacuo, affording
product. Compound 6a: mp 141.9–144.2 °C. 1H NMR
(300 MHz, CDCl3) d 2.15 (s, 6H), 2.27 (s, 3H), 6.10 (d,
J = 12.0 Hz, 1H), 6.84 (s, 2H), 7.11 (d, J = 12.0 Hz, 1H),
11.00 (s, 1H). 13C NMR (75 MHz, CDCl3) d 20.00, 20.89,
122.07, 127.89, 131.99, 134.44, 136.92, 146.28, 171.10. MS
(EI, m/z): 190 (M+). Compound 6b: mp 156.8–157.8 °C. 1H
NMR (300 MHz, CDCl3) d 6.21 (d, J = 12.0 Hz, 1H) 7.39–
7.53 (m, 4H), 7.66 (d, J = 12.0 Hz, 1H), 7.81–7.87 (m, 3H).
13C NMR (75 MHz, CDCl3) d 121.37, 124.18, 125.08,
125.97, 126.44, 126.92, 128.62, 129.15, 130.91, 132.27,
133.22, 144.66, 170.30. MS (EI, m/z): 198 (M+). Compound
6d: 217–219 °C (sublimation) 1H NMR (300 MHz, CDCl3):
d 2.13 (s, 6H, aryl-CH3), 2.19 (s, 6H, aryl-CH3), 2.22 (s, 3H,
aryl-CH3), 6.12 (d, J = 12.0 Hz, 1H, vinyl), 7.20 (d,
J = 12.0 Hz, 1H, vinyl), 10.42 (br s, 1H, COOH).
13C NMR (75 MHz, CDCl3): d 16.35, 16.76, 17.62,
121.72, 129.87, 132.22, 132.38, 134.51, 148.28, 170.38.
Compound 10a and b were reported in previous report.2h
111.5 °C 1H NMR (300 MHz, CDCl3):
d
1.12
(t, J = 7.1 Hz, 6H, CH3), 1.99 (s, 3H, aryl-CH3), 2.10
(s, 6H, aryl-CH3), 4.03 (q, J = 7.1 Hz, 4H, OCH2), 4.53
(s, 1H, OH), 6.14 (d, J = 12.0 Hz, 2H, vinyl), 7.02
(d, J = 12.0 Hz, 2H, vinyl). 13C NMR (75 MHz, CDCl3):
d 13.11, 13.87, 17.22, 59.88, 119.49, 122.49, 122.58,
133.58, 144.46, 149.51, 165.32. MS (EI, m/z): 332
(M+).
12. General procedure for the hydroarylation using propiolic
acids: after reaction, the reaction mixture was poured into
water (20 mL), neutralized by NaHCO3 and extracted with
diethyl ether (20 mL). The ethereal layer was extracted with
aqueous 2 N NaOH (10 mL) three times. A combined
water layer was washed with diethyl ether (20 mL),